Home Based Rehabilitation in Children and Adolescents with Cystic Fibrosis: A Systematic Review with Meta-Analysis and Grade Recommendations.

OBJECTIVE: The objective of this study is to elucidate the effectiveness of home based rehabilitation (HBR) and compare its results with those obtained in conventional rehabilitation (CR) programs, carried out in clinics and/or outpatient clinics. METHODS: Searches were conducted in five databases of randomized clinical trials. Study selection, data extraction, and assessment of the methodological quality of included studies were conducted independently by two reviewers, with discrepancies resolved by a third reviewer. RESULTS: The results demonstrate post-intervention values favorable to the use of HBR when compared to control group in the outcomes of forced expiratory volume in 1 second (FEV1) (MD = 14% CI: 5.42 to 22.58, p = 0.001), forced vital capacity (FVC) (MD = 8.00% CI: 0.83 to 15.17, p = 0.03) and quality of life by the Cystic Fibrosis Questionnaire - revised in the categories (Child version score" (MD= 0.71%CI: 0.15 to 1.27, p = 0.01) and "Parent version score" (MD= 0.67%CI: 0.11 to 1.23, p = 0.02). Furthermore, we noticed an increase in the distance covered in the 6-minute walk test (MD= 34.75%CI: -8.00 to 77.50, p = 0.14), in favor of HBR. CONCLUSIONS: We found that supervised or partially supervised HBR promotes improvements in FEV1, FVC and related quality of life in children and/or adolescents with cystic fibrosis.

Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment.

New coronavirus SARS-CoV-2 (COVID-19) has caused chaos in health care systems. Clinical manifestations of COVID-19 are variable, with a complex pathophysiology and as yet no specific treatment. It has been suggested that the renin-angiotensin-aldosterone system has a possible role in the severity of cases and the number of deaths. Our hypothesis is that drugs with inverse agonist effects to the angiotensin-1 receptor can be promising tools in the management of patients with COVID-19, possibly avoiding complications and the poor evolution in some cases. Any risk factors first need to be identified, and the most appropriate time to administer the drugs during the course of the infection also needs to be established. Several angiotensin receptor blockers (ARB) have a favorable profile and are important candidates for the treatment of COVID-19. In this review we discussed a set of compounds with favorable profile for COVID-19 treatment, including azilsartan, candesartan, eprosartan, EXP3174, olmesartan, telmisartan, and valsartan. They are effective as inverse agonists and could reduce the "cytokine storm" and reducing oxidative stress. As COVID-19 disease has several evolution patterns, the effectiveness of ARB therapy would be related to infection "timing", patient risk factors, previous use of ARBs, and the specific molecular effects of an ARB. However, controlled studies are needed to identify whether ARBs are beneficial in the treatment of patients with COVID-19.

Airway proteoglycans are differentially altered in fatal asthma.

It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter < or =6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (microm2)/epithelial basement membrane length (microm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 microm, C = 3.97 +/- 1.17 microm, p = 0.042; lumican: A = 1.97 +/- 0.37 microm, C = 5.66 +/- 0.99 microm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 +/- 0.84 microm, C = 5.16 +/- 0.61 microm, p = 0.045; large: A = 18.38 +/- 1.94 microm, C = 11.90 +/- 2.86 microm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma.